The goal of the proposed studies is to determine whether there is a physiological link between high blood concentrations of the branched-chain amino acids (BCAA) and pathological changes that occur in diabetes. Chronic elevation in the blood concentrations of these amino acids is observed in diabetic patients even when the concentrations of other amino acids are normal or low. There is evidence that the BCAA influence lipid and protein metabolism in isolated tissues and that pharmacological levels of the BCAA impair neural function and hormone secretion, but there is almost no information on the effects of BCAA in diabetic subjects in vivo. Using normal and streptozotocin-diabetic rats as experimental models, I shall test the hypotheses that chronic elevation in the blood concentrations of the BCAA 1) alters the turnover of catecholamines in the brain and sympathetic nervous system and 2) influences the secretion of glucagon, a hormone which antagonizes the actions of insulin. Confirmation of these hypotheses will yield new insight into the neurological and hormonal complications of diabetes mellitus and may suggest a rationale for reducing these complications.